Pigment Epithelial Derived Factor (PEDF), exhibits a number of interesting biological activities, most notably as a potent anti-neovascular or anti-angiogenic agent as well as a neurotrophic factor. The expression of Pigment Epithelial Derived Factor (PEDF) is associated with neuronal differentiation and survival factor for cells derived from the retina and central nervous system (CNS). PEDF has neurotrophic effect on neurons from areas including the cerebellum, hippocampus and spinal cord. Neurotoxicity is also often associated with administration of chemotherapeutic drugs for cancer treatment. Hence, aggressive cancer treatments are limited due to severe neurotoxicity associated with anticancer drugs. PEDF is an attractive target for gene therapy to treat a variety of neurological diseases as well as for treating tumors and other diseases associated with abnormal vascularization, e.g. age-related macular degeneration. However, prior art methods directed towards stabilizing PEDF expression in vivo have met with little success. Therefore, a need exists to develop compositions and methods that would lead to the stable expression of PEDF in vivo.